不同运动方式调控线粒体生物合成和自噬改善肥胖大鼠肾功能异常研究  

Effects of different exercise modes on relieving renal dysfunction in obese rats by regulating mitochondrial biogenesis and mitophagy

作　　者：杨青 张斌[1] 刘羽佳 李良[1] Yang Qing;Zhang Bin;Liu Yujia;Li Liang(China Institute of Sports Science,Beijing100016,China;Ordos Vocational Secondary Professional School,Erdos 017010,China)

机构地区：[1]国家体育总局体育科学研究所,北京100061 [2]鄂尔多斯市职业中等专业学校,鄂尔多斯017010

出　　处：《中国运动医学杂志》2024年第10期803-814,共12页Chinese Journal of Sports Medicine

基　　金：国家体育总局体育科学研究所基本科研业务费资助项目(基本23-54);国家体育总局体育科学研究所基本科研业务费资助项目(基本22-14、23-08)。

摘　　要：目的:观察不同运动方式对肥胖导致肾功能异常的改善效果,探讨运动调控线粒体生物合成和自噬在此过程中发挥的调控作用。方法:以5周龄雄性SD大鼠为实验对象,随机选取8只作为正常饲料安静对照组(NC组),其余大鼠饲喂高脂饲料建立肥胖导致肾功能异常大鼠模型,然后将建模成功大鼠随机分为4组:高脂饲料安静对照组(HC组)、有氧运动组(AT组)、抗阻运动组(RT组)和联合运动组(AT+RT组),每组8只。AT组大鼠使用跑台进行有氧运动,训练强度为55%~65%最大摄氧量,5 d/w,60 min/d;RT组通过爬梯法进行递增负荷抗阻运动,3 d/w,8次/d;AT+RT组进行有氧和抗阻交替运动干预,5 d/w;运动干预共持续8周。干预结束后,收集大鼠24 h尿液标本检测尿微量白蛋白(MAU);取大鼠血液样本检测血脂四项、血清肌酐(SCR)和血清胱抑素C(CysC)等指标;取附睾脂肪及肾周脂肪称重并记录;提取肾脏组织线粒体检测膜电位;苏木精伊红染色观察大鼠肾脏病理变化;Western Blot检测肾脏组织过氧化物酶体增殖物活化受体γ辅激活蛋白-1α(PGC-1α)、线粒体转录因子(Tfam)、肌球蛋白样Bcl-2结合蛋白(Beclin1)、同源性磷酸酶张力蛋白诱导激酶1(PINK1)和帕金森激酶(Parkin)的蛋白表达水平。结果:8周运动干预后,(1)AT、RT和AT+RT组大鼠的体重显著低于HC组(P<0.01);AT和RT组大鼠的Lee’s指数显著低于HC组(P<0.01,P<0.05),RT组大鼠的脂体比低于HC组(P<0.01)。(2)HC组大鼠的MAU显著高于其它4组(P<0.05)。(3)AT、RT和AT+RT组大鼠的血清甘油三酯(TG)和总胆固醇显著低于HC组(P<0.01,P<0.05),AT组的低密度脂蛋白胆固醇(LDL-C)显著低于HC组(P<0.05)。(4)AT、RT、AT+RT组大鼠的SCR显著低于HC组(P<0.05,P<0.01),RT组大鼠的SCR水平最低;AT和AT+RT组大鼠的CysC显著低于HC组(P<0.05)。(5)HC组大鼠的肾小球面积显著大于其它4组(P<0.01)。(6)NC组的大鼠肾脏细胞线粒体膜电位最高,HC组次之;AT+RTObjective To observe the effect of different exercises on relieving renal dysfunction induced by obesity,and explore their regulatory roles in mitochondrial biogenesis and mitophagy in this process.Methods Male Sprague-Dawley rats aged 5 weeks were selected as the experimental subjects.Among them,8 were randomly selected as normal diet quiet control group(NC group),while the rest were on high-fat diet to establish obesity-induced renal dysfunction.After successful modeling,they were randomly divided into a high-fat diet sedentary control group(HC group),an aerobic exercise group(AT group),a resistance training group(RT group),and a combined exercise group(AT+RT group),each of eight.The AT group underwent daily 60-minute aerobic exercise on a treadmill with an intensity of 55%-65%of the maximum oxygen uptake,5 days/week,the RT group performed progressive load resistance training using a ladder climbing method,3 days/week,8 sets/day,while the AT+RT group underwent aerobic and resistance exercise alternatingly,5 days/week,for 8 weeks successively.At the end of the intervention,24-hour urine samples were collected to test the microalbuminuria(MAU),blood samples were taken to measure lipid profile,serum creatinine(SCR),and cystatin C(CysC).Moreover,epididymal and perirenal fat were weighed and recorded,and kidney tissues were examined the mitochondrial membrane potential.Meanwhile,hematoxylin and eosin staining was used to observe pathological changes in the kidney,and Western blotting was conducted to detect the protein expression levels of peroxisome proliferator-activated receptor gamma coactivator1 alpha(PGC 1α),mitochondrial transcription factor A(Tfam),Bcl-2-interacting myosin like coiled-coil protein(Beclin1),PTEN-induced kinase1(PINK1),and Parkinson disease kinase(Parkin)in kidney tissues.Results After 8-week exercise,the body weight in the AT,RT,and AT+RT groups was significantly lower than the HC group(P<0.01).The Lee’s index in the AT and RT groups was significantly lower than the HC group(P<0.01,P<0.05)

关 键 词：运动 肾功能异常 线粒体生物合成 线粒体自噬 

分 类 号：R589.2[医药卫生—内分泌] G804.2[医药卫生—内科学]